The research proposes to investigate physiological and pharmacological mechanisms of classical conditioning using the potentiated startle effect, where acoustic startle amplitude in rats is increased in the presence of a light previously paired with a shock. In this paradigm conditioning is measured by the conditioned stimulus's (CS) effect on a reflex (acoustic startle). In the rat, the latency of acoustic startle is 8 msec. in the hindleg. We have delineated the neural pathway that mediates startle. To test where CS presentation modulates transmission along this pathway, startle will be elicited electrically at various points along the startle circuit before and after CS presentation in trained rats or control rats in which lights and shocks were randomly paired. To determine how complex the 'conditioned circuit' might be rats will be conditioned and then in testing the interval between light onset and tone onset will be varied to determine the minimum time the CS has to be on before startle is potentiated. Preliminary evidence indicates that only about 20 msec. may be required. Given retinal delays, this suggests an extraordinarily short transit time between activation of retinal ganglion cells and modification of acoustic startle. Finally, to determine the neurotransmitters involved in the expression of potentiated startle, selected drugs will be administered systemically or locally shortly before testing to see if they block or change potentiated startle.